Microfabrication technology has created new opportunities for chemical sensor design. The potential for rapid analysis and portability makes microfabricated devices attractive for applications ranging from remote chemical sensing to medical diagnostics. Microchip-based technologies for analysis of biological fluids, e.g., blood, are of significant interest.
Micro-molding in capillaries (MIMIC) is a technique for patterning organic polymer structures with micron dimensions (E. Kim, Y. Xia and G. M. Whitesides (1995) "Polymer microstructures formed by moulding in capillaries," Nature 376:581; E. Kim, Y. Xia and G. M. Whitesides (1996) J. Amer. Chem. Soc. 118:5722.) This technique is based on a mold consisting of a continuous network of channels formed when a patterned elastomeric "stamp" is brought into intimate contact with a substrate. Low-viscosity liquid pre-polymer is then placed in contact with the open ends of the channels, which spontaneously fill by capillary action. After the polymer is cured, the elastomeric master is removed, leaving a patterned polymer structure. Subsequently, more details of MIMIC technique and a variety of applications of MIMIC have been reported. See, for example, Kim, E. et al. (1997), "Solvent-assisted microcontact molding: A convenient method for fabricating three-dimensional structures on surfaces of polymers," Adv. Mat. 9(8):651; Schueller, L. J. A. et al. (1997), "Fabrication of glassy carbon microstructures by pyrolysis of microfabricated polymeric precursors," Adv. Mater. 9(6):477; Qin, D. et al. (1997), "Elastomeric light valves," Adv. Mater. 9(5):407; Xia, Y. et al. (1996), "Non-photolithographic methods for fabrication of elastomeric stamps for use in microcontact printing," Langmuir 12:4033-4038; Zhao, X.-M. et al. (1997), "Fabrication of polymeric microstructures with high aspect ratios using shrinkable polystyrene films," Adv. Mater. 9(3):251; Xia, Y. et al. (1997), "Replica molding using polymeric materials: A practical step toward nanomanufacturing," Adv. Mater. 9(2):147; Qin, D. et al. (1996), "Rapid prototyping of complex structures with feature sized larger than 20 .mu.m," Adv. Mater. 8(11):917; Zhao, X.-M. et al. (1996), "Fabrication of single-mode polymeric waveguides using micromolding in capillaries," Adv. Mater. 8(5):420; Xia, Y. et al. (1996), "Complex optical surfaces formed by replica molding against elastomeric masters," Science 273:347; Xia, Y. et al. (1996), "Micromolding of polymers in capillaries: applications in microfabrication," Chem. Mater. 8:1558.
Zhao, X.-M. et al. (1996), "Fabrication of three-dimensional microstructures: microtransfer molding," Adv. Mater. 8(10):837 report a technique related to MIMIC called microtransfer molding (.mu.TM) in which lengthwise channels in a PDMS master are filled after which the filled master is placed on a substrate. Unlike MIMIC, the technique does not rely on capillary filing of the channels. A 3:1 mixture of ethanol with a 1:2 mixture of tetraethylorthosilicate:water (pH 1, using HCl as a catalyst) was employed in the .mu.TM technique to generate SiO.sub.2 structures after solvent in the precursor was removed by heating.
Most patterning technologies allow one material to be patterned at a time. Patterning multiple materials on the same substrate normally requires sequential masking, deposition, and/or etching steps. There are a number of applications for multi-component micropatterned substrates carrying independent structures composed of different materials. MIMIC and the related .mu.TM technique provide a means for patterning a substrate with a single material. In one aspect, this invention provides a single-step molding method that can be used to pattern substrates with micro-structures of different materials.
The sol-gel process is a solution chemistry route to inorganic and inorganic-organic hybrid materials. Sol-gel processing has received a tremendous amount of research attention in the last 15 years. The physics and chemistry of the process are described in detail in the textbook: C. J. Brinker and G. W. Scherer, Sol-Gel Science: The Physics and Chemistry of Sol-Gel Processing, Boston: Academic Press, Inc., 1990. In general, the process is based on the hydrolysis and condensation of metal alkoxides, particularly silicon alkoxides. At or near ambient conditions (temperature and pressure), the process yields a gel consisting of continuous solid and fluid phases. Various processing strategies can be used to control the porous microstructure of the final solid material. A variety of sol-gel materials have been formed, with the most common being oxides. Silica has received the most attention, particularly with regard to optics applications (L. C. Klein, "Sol-Gel Optical Materials," Annu.Rev.Mater.Sci. 1993, 23,437; J. D. Mackenzie (ed.) (1994) Sol-Gel Optics III SPIE Proc. Ser. Vol. 2288, SPIE Bellingham, Wash.)
A particularly attractive feature of sol-gels is the low processing temperature, which allows the incorporation of thermally-sensitive organic molecules and functional groups into the rigid inorganic sol-gel host matrix. As a result, organically modified silicas (ORMOSILs) and organic polymer-ceramic hybrid materials (CERAMERs or Polycerams) can be formed. In addition, organics ranging from dyes to proteins to whole cells have been successfully encapsulated in sol-gel materials (See, e.g., B. K. Coltrain, C. Sanchez, D. W. Schaefer, and G. L. Wilkes (eds.)(1996) Better Ceramics Through Chemistry VII: Organic/inorganic Hybrid Materials MRS Symp. Proc. Vol 435, Mat. Res. Soc., Pittsburg, Pa.) These are particularly important for chemical and biosensor applications (O. Lev, M. Tsionsky, L. Rabinovich, V. Glezer, S. Sampath, I. Pankratov, J. Gun, Organically-modified sol-gel sensors," Anal. Chem. 1995, 67,22A; D. Avnir, S. Bram, O. Lev, and M. Ottolenghl, "Enzymes and other proteins entrapped in sol-gel materials," (1994) Chem. Mater. 6: 1605-1614; B. C. Dave, B. Dunn, J. Selverstone-Valentine, J. I. Zink, "Sol-Gel encapsulation methods for biosensors, " Anal. Chem. 1994, 66,1120A.)
The ability to pattern these hybrid materials (i.e., organic/inorganic hybrids) is critical to the development of novel micro optical device and integrated optics applications. The patterning of sol-gel materials to date has been based primarily on techniques such as laser densification (H. Krug and H. Schmidt (1994) "Organic-inorganic nanocomposites for micro optical applications", New J. Chem. 18:1125-1134; M. Yoshida and P. N. Prasad (1996) "Fabrication of channel waveguides from sol-gel processed polyvinylpyrrolidone/SiO.sub.2 composite material," Appl. Opt. 35:1500-1506); U. V. imprinting (C. Y. Li, J. Chisham, M. Andrews, S. I. Najafi, J. D. Mackenzie, and N. Peyghambarian (1995) "Sol-gel integrated optic coupler by ultraviolet light imprinting," Electronics Lett. 31:271-272); and photolithography (E. A. Mendoza, D. J. Ferrell, S. J. Syracuse, A. N. Khalil and R. A. Lieberman (1994) "Photolithography of integrated optic devices in sol-gel glasses," Sol-Gel Optics III (J. D. Mackenzie, ed.) SPIE Proc. Ser. Vol. 2288, pp 580-588, SPIE Bellingham, Wash.; C. Xu, L. Eldada, C. Wu, R. A. Norwood, L. W. Shacklette, J. T. Yardley, and Y. Wei (1996) "Photoimageable, low shrinkage organic-inorganic hybrid materials for practical multimode channel waveguides," Chem. Mater, 8:2701-2703; A. S. Holmes, R. R. A. Syms, I. Ming, and M. Green (1993) "Fabrication of buried channel waveguides on silicon substrates using spin-on glass," Appl. Optics 32:4916-4921.) Unfortunately, the radiation exposure and/or chemical treatments associated with these techniques are potentially incompatible with some hybrid sol-gel materials, particularly those containing dyes and biomolecules.
In one aspect, the invention described here is the combination of the chemical processing versatility of the sol-gel process with the fabrication versatility of MIMIC.
N. L. Jeon, P. G. Clem, R. G. Nuzzo, D. A. Payne, "Patterning of dielectric oxide thin layers by microcontact printing of self-assembled monolayers," J. Mater. Res. 1995, 10, 2996 describe methodology for patterning sol-gel layers using a technique called microcontact printing. The method employed is distinct from a capillary micro-moulding techniques in that an elastomeric stamp is first used to pattern a self-assembled monolayer (SAM) onto a sapphire substrate. A sol-gel film is then spin-coated onto the substrate. The sol-gel film has poor adhesion in the areas where the SAM has been formed. A subsequent mechanical cleaning step leaves an adherent, patterned oxide structure on the substrate. The spin-coating method described allows only one sol-gel composition to be deposited on a given substrate. PCT application WO 97/07429 "Self-assembled monolayer directed patterning of surfaces," published Feb. 27, 1997 relates to this SAM patterning method.